CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus

• Published in: PLoS pathogens 2020-04, Vol.16 (4), p.e1008242-e1008242
• Main Authors: Graziano, Vincent R, Walker, Forrest C, Kennedy, Elizabeth A, Wei, Jin, Ettayebi, Khalil, Strine, Madison S, Filler, Renata B, Hassan, Ebrahim, Hsieh, Leon L, Kim, Arthur S, Kolawole, Abimbola O, Wobus, Christiane E, Lindesmith, Lisa C, Baric, Ralph S, Estes, Mary K, Orchard, Robert C, Baldridge, Megan T, Wilen, Craig B
• Format: Article
• Language: English
• Subjects: Animals; Binding sites; Biology; Biology and life sciences; Caliciviridae Infections - virology; Departments; Epidemiology; Feces; Funding; Genomes; Health aspects; HeLa Cells; Host range; Host Specificity; Host-Pathogen Interactions; Humans; Immunology; Infection; Infections; Infectious diseases; Laboratories; Lethality; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucosa; Norovirus - growth & development; Norovirus - metabolism; Pathogenesis; Polysaccharides; Receptors; Receptors, Immunologic - metabolism; Receptors, Immunologic - physiology; Receptors, Virus - metabolism; Research and analysis methods; Stat1 protein; Tropism; Viral infections; Viral Tropism; Virology; Virus diseases; Virus-like particles; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008242

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains in vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responses in vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.